PROJECT SUMMARY ABSTRACT Healthcare-associated infections (HAIs) are a top 10 cause of death in the US. Contamination of the healthcare environment is an important but overlooked means of transmitting pathogens and HAIs, particularly gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Evidence shows that many healthcare environments are not adequately cleaned, even with institutional policies consistent with national guidance. Many issues contribute to the lack of adequate environmental cleaning. New environmental cleaning and monitoring technology and processes show some promise but evaluating them can be complex. The impact of environmental transmission and various cleaning and monitoring approaches extends beyond individual healthcare facilities and involves the dynamic ecosystem of healthcare facilities in a region. Computational modeling that integrates economic, operational, and epidemiologic components can help better understand and address the ecosystem-wide effects of environmental transmission, cleaning, and monitoring. Therefore, our proposed RHEA-MODE project will modify and substantially expand our existing Orange County (OC) and Chicago agent-based models (ABMs) to better understand healthcare environment transmission, cleaning, and monitoring. Our team is led by two seasoned investigators who have worked together for over a decade on developing ABMs to better understand the spread, impact, and control of HAIs and have over a combined 20 years of experience as Models of Infectious Disease Agent Study (MIDAS) investigators. The project will bring four major categories of additions to RHEA: (1) creating much more detailed and explicit representations of the internal structures of healthcare facilities and the movement of patients, (2) introducing healthcare worker and environmental services (EVS) staff agents in order to more explicitly represent and evaluate their actions and behaviors, (3) giving RHEA the capability of handling multiple pathogens simultaneously, because the environment and cleaning methods affect multiple pathogens at once, and (4) explicit representations of various types of environmental cleaning methods and the processes involved. Specific Aim 1 will introduce into our regional simulation models a detailed representation of the healthcare facility environment and its role in the transmission of MRSA and VRE in hospitals and nursing homes under various conditions and circumstances. Specific Aim 2 will explore how a variety of environmental cleaning products and methods can reduce MRSA and VRE transmission, prevalence, and health and economic impact based upon the expanded regional simulation models from Aim 1. Specific Aim 3 will evaluate the economic value of different combinations of environmental cleaning methods and approaches and other MRSA and VRE prevention and control measures under varying circumstances to identify the most suitable combinations utilizing the regional simulation models from Aims 1 and 2.